Endomorphin-1 (Tyr-Pro-Trp-Phe-NH2) and -2 (Tyr-Pro-Phe-Phe-NH2) are endogenous morphine-like substances that bind to the mu opiate receptor with high affinity and selectivity. These natural ligands have been shown to be as effective as morphine at reducing pain. While morphine and previously identified endogenous opiates, such as beta-endorphin and the enkephalins, have been shown to modulate neuroimmune processes, endomorphins' participation in these critical processes has not been described. My research will test the hypothesis that endomorphins are present in neurons that terminate in immunologically relevant sites including those located in peripheral organs such as the spleen, thymus, and lymph nodes as well as in the central nervous system. It is also hypothesized that during immune stress, endomorphin-1 and endomorphin-2 immunoreactivity patterns change in immune organs and in regions of the brain and spinal cord involved in stress and in immunological processes. We will also test the hypothesis that central administration of endomorphins modulates immune function, but produces less immunosuppression than morphine.